The objective of this research project is to study the structure and function, both chemical and biological, of the three citrate lyase enzymes. The citrate lyase from bacteria will be studied in relation to: 1) its function as a multi-enzyme complex, 2) the structure and biosynthesis of its newly characterized prosthetic group (phosphoribosyl dephospho CoA) and 3) its biological control by its activating enzyme (a ligase) and its inactivating enzyme (a deacetylase). Citrate synthases from eucaryotes will be investigated in relation to: 1) the possible involvement of SH groups in its mechanism and 2) its location within the mitochondrial matrix and its possible functioning as part of a "Krebs cycle multi-enzyme complex." Finally, ATP citrate lyase from rat liver will be studied to determine: 1) the subunit and "domain" structure of the enzyme and their relationship to the partial reactions of the enzyme and 2) the intracellular functioning of the enzyme with acetyl CoA carboxylase and fatty acid synthetase as part of a putative complex for fatty acid synthesis.